ArticlemBio2025
An investigation of gene dosage reveals that increased sensitivity to D-cycloserine divergently impacts the transience of heteroresistance in
Article in mBio, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Heteroresistance describes the phenomenon where seemingly isogenic bacterial populations contain subpopulations with elevated resistance compared to the susceptible majority that are often missed in routine susceptibility testing. The enhanced resistance of those subpopulations can either be maintained (stable) or quickly lost (unstable/transient) after treatment, where transient cases return susceptibility results identical to those of original cultures. Recent work has implicated increased gene dosage of resistance determinants as a major cause of unstable heteroresistance in clinical isolates. Inspired by that work, we sought to systematically evaluate how gene dosage of an antibiotic's target network components impacted heteroresistance and its stability. To accomplish that, we used IMPORTANCE: Heteroresistance is a concern because heteroresistant strains escape clinical detection and facilitate treatment failure. Heteroresistant cells can produce stably resistant or transiently resistant populations, and enhanced understanding of genetic factors that influence the level of heteroresistance and its stability has the potential to improve treatment strategies. Here, we introduce the heteroresistance stability index, which is a quantitative metric of heteroresistance stability, and use it to analyze heteroresistance of
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